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Molecular Neurobiology

, Volume 55, Issue 5, pp 4373–4387 | Cite as

Gestational Hypothyroxinemia Imprints a Switch in the Capacity of Astrocytes and Microglial Cells of the Offspring to React in Inflammation

  • María C. Opazo
  • Pablo A. González
  • Betsi D. Flores
  • Luis F. Venegas
  • Eduardo A. Albornoz
  • Pablo Cisternas
  • Karen Bohmwald
  • Pamela A. Nieto
  • Susan M. Bueno
  • Alexis M. Kalergis
  • Claudia A. Riedel
Article

Abstract

Hypothyroxinemia (Hpx) is a highly frequent condition characterized by low thyroxine (T4) and normal 3,3′,5′-triiodothyronine (T3) and thyroid stimulating hormone (TSH) levels in the blood. Gestational Hpx is closely related to cognitive impairment in the human offspring. In animal models gestational Hpx causes impairment at glutamatergic synapsis, spatial learning, and the susceptibility to suffer strong autoimmune diseases like experimental autoimmune encephalomyelitis (EAE). However, the mechanisms underlying these phenotypes are unknown. On the other hand, it has been shown that astrocytes and microglia affect the outcome of EAE. In fact, the activation of astrocytes and microglia in the central nervous system (CNS) contributes to EAE progression. Thus, in this work, the reactivity of astrocytes and microglia from rats gestated in Hpx was evaluated aiming to understand whether these cells are targets of gestational Hpx. Interestingly, microglia derived from the offspring gestated in Hpx were less reactive compared to microglia derived from offspring gestated in euthyroidism. Instead, astrocytes derived from the offspring gestated in Hpx were significantly more reactive than the astrocytes from the offspring gestated in euthyroidism. This work contributes with novel information regarding the effects of gestational Hpx over astrocytes and microglia in the offspring. It suggests that astrocyte could react strongly to an inflammatory insult inducing neuronal death in the CNS.

Keywords

Gestational hypothyroxinemia Microglia Astrocytes Neuron EAE 

Notes

Acknowledgements

This work was supported by funding from the Millennium Institute on Immunology and Immunotherapy from Chile (P09/016-F for MCO, CR, SB, and AMK), FONDECYT POSTDOCTORADO 3130539, FONDECYT 1130996, FONDECYT 1161525, FONDECYT 1110604, FONDECYT 1150862, Núcleo UNAB DI-741-15/N, and Beca de Doctorado Nacional (CONICYT) (LFV, KAB, and PAN).

Supplementary material

12035_2017_627_MOESM1_ESM.jpg (208 kb)
Supplemental figure 1: Increased T3/T4 ratio in the MMI treated pregnant dams. Scatter plot of the T3/T4 ratio calculated for control, Hpx and Hpx+T4 pregnant dams. A significant increase of this ratio was observed in Hpx pregnant mice consistent with an altered thyroid function induced by the MMI treatment. ANOVA and Tukey’s Post test. Different letters indicate significant differences at p<0.05 (n=4) (JPEG 208 kb).

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • María C. Opazo
    • 1
    • 2
  • Pablo A. González
    • 1
    • 2
  • Betsi D. Flores
    • 1
    • 2
  • Luis F. Venegas
    • 1
    • 2
  • Eduardo A. Albornoz
    • 1
    • 2
  • Pablo Cisternas
    • 1
    • 2
  • Karen Bohmwald
    • 2
    • 3
  • Pamela A. Nieto
    • 2
    • 3
  • Susan M. Bueno
    • 2
    • 3
  • Alexis M. Kalergis
    • 2
    • 3
  • Claudia A. Riedel
    • 1
    • 2
  1. 1.Laboratorio de Biología Celular y Farmacología, Facultad de Ciencias Biológicas y Facultad de MedicinaUniversidad Andres BelloSantiagoChile
  2. 2.Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias BiológicasPontificia Universidad Católica de ChileSantiagoChile
  3. 3.Departamento de Endocrinología, Facultad de MedicinaPontificia Universidad Católica de ChileSantiagoChile

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